Lectins, particularly Concanavalin A, have been used to study topographical changes of membrane surfaces in a variety of cell lines and under various physiological conditions. Various lectins differ with respect to their agglutination or mitogenic abilities even within the same cell line, therefore reflecting important differences in their structure-function relationships. It has recently been reported that Con A will inhibit the binding of LDL to cultured human fibroblasts and will subsequently prevent the fusion of cholesterol containing endocytic particles with lysosomes. We propose to study the mechanism of these processes, using a variety of selected lectins and certain chemically modified derivatives of Concanavalin A, using both normal and familial hypercholesterolemic human fibroblasts. In addition, we have developed, through collaborative efforts, a unique 113Cd derivative of Con A, which, using NMR techniques, can distinguish between low and high molecular weight carbohydrate moeities which will allow model studies of Con A interactions more closely related to in vivo lectin-cell interaction.